A variety of methods are currently available for making arrays of biological macromolecules, such as arrays of nucleic acid molecules or proteins. One method for making ordered arrays of DNA on a porous membrane is a "dot blot" approach. In this method, a vacuum manifold transfers a plurality, e.g., 96, aqueous samples of DNA from 3 millimeter diameter wells to a porous membrane. This method is not suitable for making microarrays, i.e., arrays in which the different sample regions in the array are separated by distances of about 1 mm or less.
Microarrays may be made by a robotic arm device that moves successively between a sample-pickup well in a sample array, e.g., a microtitre plate, and a selected microarray position. Although high-density arrays of different biological materials can be constructed by this approach, the production time and efficiency is limited by the fact that the regions of the microarray (or microarrays, if several are being constructed at once) are deposited one-by-one in serial fashion.
Methods for making oligomer arrays on a microchip by parallel step-wise subunit addition have been proposed, e.g., Fodor, et al., Science 251:767-773 (1991). This approach uses photomasking to selectively deprotect terminal subunit addition sites in selected regions of the array thus allowing massive parallel subunit addition in building the oligomers on the array. This approach, however, requires relatively expensive processing equipment. It is also not readily adapted to constructing arrays of polymers that are more than about 10-15 subunits in length.
It would therefore be desirable to provide an improved method and apparatus for making arrays, particularly microarrays, employing parallel sample deposition.